MRI diffusion coefficients in spinal cord correlate with axon morphometry

Abstract

Following spinal cord injury, diffusion MRI (DWI) has been shown to detect injury and functionally significant neuroprotection following treatment that otherwise would go undetected with conventional MRI. The underlying histologic correlates to directional apparent diffusion coefficients (ADC) obtained with DWI have not been determined, however, and we address this issue by directly correlating ADC values with corresponding axon morphometry in the normal rat cervical spinal cord. ADC values transverse (perpendicular) and longitudinal (parallel) to axons both correlate with axon counts, however each directional ADC reflects distinct histologic parameters. DWI may therefore be capable of providing specific histologic data regarding the integrity of white matter.

Brain microstructural correlates of visuospatial choice reaction time in children

“…Further, parallel ADC was found to be positively correlated with axonal diameter, and negatively with axonal number (Schwartz et al, 2005). It should be noted that other tissue parameters, such as axon density and tortuosity, crossing fibres and tract geometry may also contribute to differences in λ⊥ and λ || (Beaulieu, 2009;Schwartz et al, 2005). Whatever the neuroanatomical correlate of λ⊥ or λ || might be, our observation of similar effects of λ⊥ and λ || provides no further evidence regarding the cellular basis of these effects.…”

“…Moreover, a study of the normal rat cervical spinal cord found that the perpendicular apparent diffusion coefficient (ADC), a measure similar to MD, was positively correlated with extracellular volume fraction and axonal spacing, and negatively correlated with axonal number and myelination. Further, parallel ADC was found to be positively correlated with axonal diameter, and negatively with axonal number (Schwartz et al, 2005). It should be noted that other tissue parameters, such as axon density and tortuosity, crossing fibres and tract geometry may also contribute to differences in λ⊥ and λ || (Beaulieu, 2009;Schwartz et al, 2005).…”

“…These findings may explain why we only observed effects of CST MD, and not of CST FA. Although interpretation of differences in DTI parameters is not straightforward, some studies suggest that λ⊥ may be more sensitive to changes in myelination, extracellular volume fraction, and axonal density (Schwartz et al, 2005;Song et al, 2003Song et al, , 2005, whilst λ || may be more sensitive to differences in axonal diameter (Schwartz et al, 2005). Using a mouse model of retinal ischemia, a DTI and histology study revealed a gradual decrease in relative anisotropy, caused by, at first, decrease in λ || , corresponding with the timing of axonal degeneration, followed by increase in λ⊥, associated with optic nerve demyelination (Song et al, 2003).…”

Indirect measurement of regional axon diameter in excised mouse spinal cord with q-space imaging: Simulation and experimental studies

“…However, if it were coupled with information on ECS and ICS volume fractions, new insights into axonal architecture can be gained such as an estimate of the axon count, an important parameter in determining function after spinal cord injury (Schwartz et al, 2005b) or quantification of axon loss, which would affect the ECS and ICS volume fractions, and demyelination, which would increase the displacement profile FWHM, both of which are hallmarks of spinal cord injury and a variety of WM diseases from multiple sclerosis to Alzheimer's disease (Budde et al, 2007;Horsfield and Jones, 2002). FWHM and zero-displacement probability have been observed to increase and decrease, respectively, in the presence of axon loss and demyelination (Assaf et al, 2002a), which we have also observed in ICS-weighted simulations of synthetic circular axons exhibiting only 10% axonal loss (data not shown).…”

“…Recent work has used DWI to investigate regional axon architecture (Schwartz et al, 2005a;Schwartz et al, 2005b). Schwartz et al performed ex vivo DWI of normal adult rat cervical spinal cords and computed transverse ADC (tADC) maps and longitudinal ADC (lADC) maps, i.e.…”